Sudden Death in Indeterminate Chagas disease is Uncommon. A Systematic Review

La enfermedad de Chagas es un problema sanitario de gran magnitud en América Latina debido a su alta prevalencia, morbilidad y mortalidad. A su vez, las migraciones desde los países latinoamericanos hacia los Estados Unidos y Europa han dispersado a una cantidad significativa de personas portadoras de la enfermedad. Es importante tener en cuenta que la mayoría de los pacientes permanecen en la forma indeterminada de la enfermedad por décadas, sin manifestar ningún síntoma ni signo de su afección. A pesar de ello, hay quienes sostienen que la forma indeterminada conlleva un aumento del riesgo de padecer muerte súbita, aunque no hay estudios que se hayan diseñado específicamente a fin de esclarecer esta cuestión. En una revisión sistemática de los estudios con seguimiento de pacientes chagásicos asintomáticos con ECG normal y de causa conocida de muerte encontramos 15 artículos que incluyen el seguimiento de 9.382 pacientes. La mortalidad entre los asintomáticos con ECG normal fue muy baja (0,92%), que no resultó estadísticamente diferente de la de los controles no chagásicos (p = 0,38). Esta revisión sistemática muestra que la muerte súbita es infrecuente en la forma indeterminada. Estos pacientes tienen el mismo riesgo que la población general y por lo tanto se les debe permitir que lleven una vida normal tanto en el aspecto laboral como en lo relativo a su actividad física, sin alarmarlos innecesariamente sobre su condición clínica ni abrumarlos con estudios sofisticados y costosos. Es necesario, sin embargo, el control periódico, ya que si el paciente progresa a la forma cardíaca el riesgo de muerte aumenta notablemente.Chagas disease is a serious health care problem in Latin America due to its high prevalence, morbidity and mortality. The migration from Latin American countries to the United States and Europe has disseminated a significant number of infected subjects. Most patients present the indeterminate form of the disease and remain without symptoms for decades. However, some groups believe that patients with the indeterminate form are at high risk for developing sudden death although no studies have been designed to investigate this issue. We conducted a systematic review of follow-up studies in patients with asymptomatic Chagas disease, normal ECG and known cause of death. We found 15 articles including 9382 patients. Mortality rate in asymptomatic patients with normal ECG was very low (0.92%) and similar to that of controls without Chagas disease (p=0.38). This systematic review shows that sudden death is uncommon in the indeterminate form of the disease and that the risk of death is similar to that of the general population. Thus, these patients should be allowed to lead a normal working life and to practice physical activity, without alarming them unnecessarily about their condition or indicating sophisticated and expensive studies. Regular follow-up is necessary as the death risk increases considerably when the disease progresses to the cardiac form.Fil: Gonzalez, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Azzato, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); ArgentinaFil: Ambrosio, Giuseppe. Universita Di Perugia; ItaliaFil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentin

Antioxidants supplementation in elderly cardiovascular patients

Supplementation with antioxidants and its benefit-risk relationship have been largely discussed in the elderly population. We evaluated whether antioxidants supplementation improved the biochemical profile associated with oxidative metabolism in elderly cardiovascular patients. Patients (n = 112) received daily supplementation with α-TP 400 mg, beta-carotene 40 mg, and vitamin C 1000 mg for 2 months (treatment). Plasma concentrations of alpha-tocopherol (α-TP), β-carotene (βC), ubiquinol-10 (QH-10), glutathione, and thiobarbituric acid reactive substances (TBARS) were determined before and after treatment. Response to treatment was dependent on pretreatment α-TP and βC levels. Increase in α-TP and βC levels was observed only in patients with basal levels <18 μM for α-TP (P < 0.01) and <0.30 μM for βC (P < 0.02). Ubiquinol-10, glutathione, and TBARS were unaffected by treatment: QH-10 (+57%, F(1,110) = 3.611, P < 0.06, and N.S.), glutathione (+21%, F(1,110) = 2.92, P < 0.09, and N.S.), and TBARS (-29%, F(1,110) = 2.26, P < 0.14, and N.S.). Treatment reduced oxidative metabolism: 5.3% versus 14.6% basal value (F(1,110) = 9.21, P < 0.0003). Basal TBARS/α-TP ratio was higher in smokers compared to nonsmokers: 0.11 ± 0.02 versus 0.06 ± 0.01 (F(32,80) = 1.63, P < 0.04). Response to antioxidant supplementation was dependent on basal plasma levels of α- TP and βC. Smoking status was strongly associated with atherosclerotic cardiovascular disease and high TBARS/α-TP ratio (lipid peroxidation).Fil: Otero Losada, Matilde. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentina;Fil: Vila, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentina;Fil: Azzato, F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentina;Fil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentina

Oxidative stress and mitochondrial damage in coronary artery bypass graft surgery: Effects of antioxidant treatments

We examined antioxidant actions in 73 patients undergoing coronary artery surgery by assessing mitochondrial damage and oxidative stress in ventricular biopsies obtained at preischemia and postreperfusion. Those patients who received antioxidant therapy benefited by less oxidative stress and mitochondrial damage.Fil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Ferreira, Ricardo. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Grana, Daniel Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Boveris, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Exercise Ameliorates Endocrine Pancreas Damage Induced by Chronic Cola Drinking in Rats

Purpose: This study evaluates whether the daily practice of an exercise routine might protect from endocrine pancreas damage in cola drinking rats. Methods: Forty-eight Wistar rats were randomly assigned to 4 groups depending on a) beverage consumption ad libitum, water (W) or cola beverage (C), and b) physical activity, sedentary (S) or treadmill running (R). Accordingly, 4 groups were studied: WS (water sedentary), WR (water runner), CS (cola sedentary) and CR (cola runner). Body weight, nutritional data, plasma levels of glucose, creatinine, total cholesterol and cholesterol fractions, and triglycerides (enzymocolorimetry), and systolic blood pressure (plethysmography) were measured. After 6 months, euthanasia was performed (overdose sodium thiopental). Pancreatic tissue was immediately excised and conventionally processed for morphometrical and immunohistochemical determinations. Results: The effects of running and chronic cola drinking on pancreas morphology showed interaction (p<0.001) rather than simple summation. Cola drinking (CS vs WS) reduced median pancreatic islet area (-30%, 1.8 104 μm2 vs 2.58 104 μm2, p<0.0001) and median β-cell mass (-43%, 3.81 mg vs 6.73 mg, p<0.0001), and increased median α/β ratio (+49%, 0.64 vs 0.43, p< 0.001). In water drinking rats (WR vs WS), running reduced median α-cell mass (-48%, 1.48 mg vs 2.82 mg, p<0.001) and α/β ratio (-56%, 0.19 vs 0.43, p<0.0001). Differently, in cola drinking rats (CR vs CS), running partially restored median islet area (+15%, 2.06 104 μm2 vs 1.79 104 μm2, p<0.05), increased median β-cell mass (+47%, 5.59 mg vs 3.81 mg, p <0.0001) and reduced median α/β ratio (-6%, 0.60 vs 0.64, p<0.05). Conclusion: This study is likely the first reporting experimental evidence of the beneficial effect of exercise on pancreatic morphology in cola-drinking rats. Presently, the increase of nearly 50% in β cells mass by running in cola drinking rats is by far the most relevant finding. Moderate running, advisably indicated in cola consumers and patients at risk of diabetes, finds here experimental support.Fil: Otero-Losada, Matilde Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Gonzalez, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Muller, Maria Angelica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Ottaviano, Graciela Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Azzato, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Ambrosio, Giuseppe. Università di Perugia; ItaliaFil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentin

Inflammatory cells, apoptosis and Chlamydia pneumoniae infection in atherosclerosis

Chlamydia pneumoniae (CP), chromosomal alterations and apoptosis were suggested as contributing factors in the pathogenesis of atherosclerosis. Early (EP) and unstable plaques (UP) were studied in order to assess infiltrate composition, the apoptotic index, chromosome 7 stability and to investigate the concurrent presence of CP in EP and UP. Paraffin embedded sections of three iliac arteries and four aortas from young donors (EP), and four coronaries and nine carotid arteries (UP) were used. Aside from histological techniques, immunophenotypification for macrophages, T and B cells, smooth muscle and endothelial cells; FISH and DNA nick end labeling were performed. The amplifications with PCR for CP infection were negative in all specimens. In the EP, a focal myointimal thickening with foam cells and scarce smooth muscle cells was observed. Macrophages were most frequent in the intima (10.8%) while T and B cells were found in 2.3 and 1.5%. In the UP a thin cap covering a lipid-rich core with widespread vascularization and with severe luminal obstruction was observed. Macrophages were increased (21%), and T (1.5%) and B cells (3.5%) in the caps and inner areas of the lipid cores. At these sites, the FISH showed trisomy and tetrasomy of chromosome 7 and apoptosis was very frequent (10-30%). Macrophages in intimal lesions is one of the most prominent, consistent and permanent features in EP, and an elevated apoptotic index and chromosome 7 instability might contribute to evolution from stable to complicated plaques, while CP seems to play no role. However, further studies are needed with more cases to confirm this last observation. Copyright (C) 2000 Elsevier Science Ireland Ltd.Fil: Matturri, Luigi. Università degli Studi di Milano; Italia. IRCCS Ospedale Maggiore; ItaliaFil: Cazzullo, Alessandra. Università degli Studi di Milano; Italia. IRCCS Ospedale Maggiore; ItaliaFil: Turconi, Paola. IRCCS Ospedale Maggiore; Italia. Università degli Studi di Milano; ItaliaFil: Roncoroni, Lucia. IRCCS Ospedale Maggiore; Italia. Università degli Studi di Milano; ItaliaFil: Grana, Daniel Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina. Universidad del Salvador. Facultad de Medicina; ArgentinaFil: Milei, Jose. Universidad del Salvador. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentin

Cardiorenal Involvement in Metabolic Syndrome Induced by Cola Drinking in Rats: Proinflammatory Cytokines and Impaired Antioxidative Protection

We report experimental evidence confirming renal histopathology, proinflammatory mediators, and oxidative metabolism induced by cola drinking. Male Wistar rats drank ad libitum regular cola (C, = 12) or tap water (W, = 12). Measures. Body weight, nutritional data, plasma glucose, cholesterol fractions, TG, urea, creatinine, coenzyme Q10, SBP, and echocardiograms (0 mo and 6 mo). At 6 months euthanasia was performed. Kidneys were processed for histopathology and immunohistochemistry (semiquantitative). Compared with W, C rats showed (I) overweight (+8%, < 0.05), hyperglycemia (+11%, < 0.05), hypertriglyceridemia (2-fold, < 0.001), higher AIP (2-fold, < 0.01), and lower Q10 level (−55%, < 0.05); (II) increased LV diastolic diameter (+9%, < 0.05) and volume (systolic +24%, < 0.05), posterior wall thinning (−8%, < 0.05), and larger cardiac output (+24%, < 0.05); (III) glomerulosclerosis (+21%, < 0.05), histopathology (+13%, < 0.05), higher tubular expression of IL-6 (7-fold, < 0.001), and TNF (4-fold, < 0.001). (IV) Correlations were found for LV dimensions with IL-6 (74%, < 0.001) and TNF (52%, < 0.001) and fully abolished after TG and Q10 control. Chronic cola drinking induced cardiac remodeling associated with increase in proinflammatory cytokines and renal damage. Hypertriglyceridemia and oxidative stress were key factors. Hypertriglyceridemic lipotoxicity in the context of defective antioxidant/anti-inflammatory protection due to low Q10 level might play a key role in cardiorenal disorder induced by chronic cola drinking in rats.Fil: Otero-Losada, Matilde Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Gómez Llambí de Oromí, Hernán Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Ottaviano, Graciela Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Muller, Maria Angelica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Azzato, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Ambrosio, Giuseppe. Università di Perugia; ItaliaFil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentin

Coronary Intimal Thickening: Once Again

In a letter to the Editor, Briana and Malamitsi-Puchner1 commented our recently published paper in which we showed that intimal thickening already begins in fetal life and progresses through childhood and adolescence.2 Our work is in line with studies by Barker about the fetal origins of adult disease which led to The Barker Hypothesis, indicating that the pathogenesis of cardiovascular (CV) disease begins in utero.3Briana et al.1 recently evaluated cord blood serum for potentially prognostic biomarkers for CV disease in large-for-gestational-age compared with appropriate-for-gestational-age neonates. Among other biomarkers, the authors studied serum cardiotrophin-1, a cardiomyocyte-produced chemokine that plays a fundamental role in fetal heart development and whose expression is increased by hypoxia, mechanical stress and proinflammatory cytokines such as interleukin (IL) 1b. The authors1 also studied serum levels of cardiac myocytesarcomeral protein titin, involved in sensing and responding to myocardial stress. As a result, Briana et al.1 propose that cord blood serum concentrations of both cardiotrophin-1 and titin could represent prognostic biomarkers for future CV disease.4In addition, another study by Milei et al.5 analyzed autopsy heart samples from 22 fetal sudden intrauterine death and 36 sudden infant death victims, all between the 32nd week of gestation and 1year of age. In 28 out of 58 cases, the mothers were smokers. Coronary lesions were detected in 10 of 12 fetuses and in 15 of 16 infants whose mothers smoked, while only 5cases (2 of 10 fetuses and 3 of 20 infants) arterial lesions were found in cases of nonsmoking mothers (p 1 artery, compared with 25% in the CoHD patients without surgery (p<0.001). Hence, these results suggest a higher rate of coronary intimal hyperplasia in surgically repaired CoHD patients as compared with non-repaired ones.6 This high incidence was correlated with intimal decrease in estrogen receptor α (ERα) expression, an increment in transforming growth factor β1 (TGF-β1) expression and in apolipoprotein B (apoB) deposition, which allowed us to conclude that a decrease in ERα and augmented expression of TGF-β1 expression may contribute to the development of atherosclerotic coronary artery disease in CoHD patients.6,7 A case report illustrating our findings described an aneurysm in the left main coronary artery of a 2-year-old patient. This aneurysm presented intimal hyperplasia and strong apoB deposition.8As mentioned in the Briana and Malamitsi-Puchner letter,1 it is important to search for early biomarkers of CV disease at an early age in order to implement preventive strategies. In this regard, we suggest that special attention should be given to children of smoking mothers and to CoHD patients, particularly if they underwent reparative surgery.Fil: Castilla Lozano, Maria del Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Gutierrez, Christopher P. A.. Universidad de Buenos Aires; ArgentinaFil: Azzato, Francisco. Universidad de Buenos Aires; ArgentinaFil: Ambrosio, Giuseppe. Università di Perugia; ItaliaFil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentin

Coronary Intimal Thickening Begins in Fetuses and Progresses in Pediatric Population and Adolescents to Atherosclerosis

The prevalence of coronary intimal thickening (IT) was assessed in fetuses and pediatric population. We studied the coronary arteries of 63 hearts obtained from fetuses, infants, children, and adolescents, deceased from noncardiac disease or trauma. Histomorphometric analysis, planimetry, and immunohistochemical studies were conducted. Intimal thickening consisted of proliferation of smooth muscle cells and scarce monocytes embedded in amorphous deposits within the internal elastic membrane (IEM). Intermingled lesions of intimal hyperplasia and parietal nonstenotic plaques were also observed. Intimal thickening was found in 10% of 20 fetuses, in 33.3% of 18 infants, 73.3% of 15 children, and 100% of 10 adolescents. A significant correlation (r = 0.671, P < 0.001) was found between the extent of IT and age. The IEM was duplicated or interrupted in 43% of patients, showing a positive correlation with the degree of IT (P = 0.01). Intimal thickening was predominantly found near bifurcation sites in the left anterior descending coronary artery (55.6%) and in zones free of bifurcation in the right coronary artery (75%). In conclusion, the prevalence and extension of IT lesions are higher at older ages within a young population. Intimal thickening may be regarded as the first event occurring in coronary preatherosclerosis, preceding lipid deposition.Fil: Guerri Guttenberg, Roberto Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Castilla, Rocio Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Azzato, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Ambrosio, Giuseppe. Università di Perugia; ItaliaFil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentin

Cardioprotection after acute exposure to simulated high altitude in rats: Role of nitric oxide

Aim In previous studies, upregulation of NOS during acclimatization of rats to sustained hypobaric hypoxia was associated to cardioprotection, evaluated as an increased tolerance of myocardium to hypoxia/reoxygenation. The objective of the present work was to investigate the effect of acute hypobaric hypoxia and the role of endogenous NO concerning cardiac tolerance to hypoxia/reoxygenation under β-adrenergic stimulation. Methods Rats were submitted to 58.7 kPa in a hypopressure chamber for 48 h whereas their normoxic controls remained at 101.3 kPa. By adding NOS substrate L-arg, or blocker L-NNA, isometric mechanical activity of papillary muscles isolated from left ventricle was evaluated at maximal or minimal production of NO, respectively, under β-adrenergic stimulation by isoproterenol, followed by 60/30 min of hypoxia/reoxygenation. Activities of NOS and cytochrome oxidase were evaluated by spectrophotometric methods and expression of HIF1-α and NOS isoforms by western blot. Eosin and hematoxiline staining were used for histological studies. Results Cytosolic expression of HIF1-α nNOS and eNOS, and NO production were higher in left ventricle of hypoxic rats. Mitochondrial cytochrome oxidase activity was decreased by hypobaric hypoxia and this effect was reversed by L-NNA. After H/R, recovery of developed tension in papillary muscles from normoxic rats was 51–60% (regardless NO modulation) while in hypobaric hypoxia was 70% ± 3 (L-arg) and 54% ± 1 (L-NNA). Other mechanical parameters showed similar results. Preserved histological architecture was observed only in L-arg papillary muscles of hypoxic rats. Conclusion Exposure of rats to hypobaric hypoxia for only 2 days increased NO synthesis leading to cardioprotection.Fil: la Padula, Pablo Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Etchegoyen, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Czerniczyniec, Analia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Piotrkowski, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Silvia LoresArnaiz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Milei, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Costa, Lidia Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentin